US4996292A - Self-sealing artificial skin comprising copoly-alpha-amino acid - Google Patents
Self-sealing artificial skin comprising copoly-alpha-amino acid Download PDFInfo
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- US4996292A US4996292A US07/373,503 US37350389A US4996292A US 4996292 A US4996292 A US 4996292A US 37350389 A US37350389 A US 37350389A US 4996292 A US4996292 A US 4996292A
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- self
- artificial skin
- mixture
- copolyamino
- lysine
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- 238000007789 sealing Methods 0.000 title claims abstract description 12
- 229920001577 copolymer Chemical class 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 22
- 150000007513 acids Chemical class 0.000 claims abstract description 14
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 15
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 12
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 11
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 7
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 7
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 7
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 7
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 7
- 239000004471 Glycine Substances 0.000 claims description 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 6
- 239000004473 Threonine Substances 0.000 claims description 6
- 229960000310 isoleucine Drugs 0.000 claims description 6
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims 5
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 5
- 239000004472 Lysine Substances 0.000 claims 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 5
- 235000004279 alanine Nutrition 0.000 claims 5
- 150000001371 alpha-amino acids Chemical class 0.000 claims 5
- 235000008206 alpha-amino acids Nutrition 0.000 claims 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 5
- 235000009697 arginine Nutrition 0.000 claims 5
- 235000003704 aspartic acid Nutrition 0.000 claims 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims 5
- 235000018417 cysteine Nutrition 0.000 claims 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 5
- 235000013922 glutamic acid Nutrition 0.000 claims 5
- 239000004220 glutamic acid Substances 0.000 claims 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 5
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims 5
- 229960003646 lysine Drugs 0.000 claims 5
- 235000018977 lysine Nutrition 0.000 claims 5
- 229930182817 methionine Natural products 0.000 claims 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 5
- 239000004474 valine Substances 0.000 claims 5
- 229960005337 lysine hydrochloride Drugs 0.000 claims 2
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- 150000001413 amino acids Chemical group 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 4
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 4
- 229960005261 aspartic acid Drugs 0.000 description 4
- 229960002989 glutamic acid Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 239000005297 pyrex Substances 0.000 description 2
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 229930182844 L-isoleucine Natural products 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 238000004347 surface barrier Methods 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
- C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
- C08G69/10—Alpha-amino-carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
Definitions
- This invention relates to the field of protein engineering in general, and to the fields of thermal protein engineering and dermatology in particular.
- Bioly generated proteins are copolyamino acids which have been synthesized on cellular ribosomes with amino acid sequences that are directed by nucleic acids.
- Thermal copolyamino acids form a class of thermally engineered proteins (TEPs) because they possess amino acid sequences that have not been currently found in nature. They sometimes are referred to as proteinoids to reflect the fact that, although they resemble proteins structurally and functionally, they are produced abiotically in contrast to biologically generated proteins such as collagen, to use just one example. They are also referred to as thermal proteins for the same reason. Organisms do not make proteins by heating amino acids.
- Proteinoids or TEPS, are much easier to make than proteins which are engineered by genetic means or by standard organic synthetic means.
- the object of this invention was to make a self-sealing artificial skin from thermal copolyamino acids, or TEps, that could mimic some of the proerties of biological skins.
- TEPs thermal copolyamino acids
- proteinoids also known as proteinoids or thermally engineered proteins
- Thermal copolyamino acid PB V 5 (1) was prepared as follows. L-Aspartic acid (100 g), L-glutamic acid (100 g), and an equimolar mixture (50 g) of L-alanine, L-arginine, L-cysteine, glycine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine, and L-valine, were mixed together and then placed in a flask. The flask containing the amino acid mixture was then heated in an oil bath at 190° C. for 6 hrs. under a nitrogen atmosphere.
- Thermal copolyamino acid PB V 5 (2) was prepared in a similar fashion except that 100 g of L-aspartic acid, 100 g of L-glutamic acid, and 100 g of the equimolar basic neutral (BN) amino acid mixture referred to above was used.
- Thermal copolyamino acid PB V 5 (3) was prepared in a similar fashion except that 50 g of L-aspartic acid, 50 g of L-glutamic acid, 50 g of BN mix, and 50 g of L-lysine hydrochloride was used.
- Thermal copolyamino acid PB V 5 (4) was prepared in a similar fashion except that 50 g of L-aspartic acid, 50 g of L-glutamic acid, 50 g of BN mix, and 100 g of L-lysine hydrochloride was used and the flask was heated at 195° C. instead of 190° C.
- the PB V 5 (1) thermal copolyamino acid is also referred to as a 2:2:1 Asp:Glu:BN TEP
- the PB V 5 (2) thermal copolyamino acid is referred to as a 1:1:1 Asp:Glu:BN TEP
- the PB V 5 (3) thermal copolyamino acid is referred to as a 1:1:1:1 Asp:Glu:BN:Lys TEP
- the PB V 5 (4) thermal copolyamino acid is referred to as a 1:1:1:2 Asp:Glu:BN:Lys TEP.
- the resulting yields of the various TEPs were: 75 g of 2:2:1 TEP, 11 g of 1:1:1 TEP, 11 g of 1:1:1:1 TEP, and 11 g of 1:1:1:2 TEP.
- the yield is lower than expected because some of the 1:1:1 preparation formed a tar-like liquid upon addition of water. This was discarded along with the soluble fraction.
- Distilled water (1500 ml) was added to each of the water-insoluble TEP fractions (1.5 g-6.0 g) in 2000 ml beakers.
- the beakers were heated over a large Bunsen burner until the contents were vigorously boiling. At this point, sticky portions of the TEPs adhered to the sides of the beakers. These portions were discarded.
- the hot colored soutions were decanted into a second set of 2000 ml beakers. Then the hot solutions were poured into 8 in. by 8 in. square Pyrex baking dishes (500 ml per dish). The dishes were allowed to cool slowly to room temperature without being disturbed.
- the TEP skins can be picked up and applied to the surface of any object which is placed in the TEP solution and gently lifted out of the TEP solution from underneath the surface of the TEP skin.
- the skin thereupon dries on the surface of the subject object. This procedure can be repeated a number of times to build up several laminate layers of the skin upon a subject object. It was also found that the thickness of the skin which forms upon the surface of the TEP solutions is proportional to the concentration of proteinoid used in the preparation of the hot TEP solution.
- the self-sealing artificial TEP skins can be applied to any surface where a dry, biologically compatible surface barrier against foreign matter is desired. Such undesirable foreign matter includes dust, dirt, and microbes. Artificial skins of this type have many applications, among them the dressing of mammalian burn wounds.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
Thermally polymerized copolyamino acids are used to make a biologically compatible self-sealing skin.
Description
This invention relates to the field of protein engineering in general, and to the fields of thermal protein engineering and dermatology in particular.
It has long been recognized that the skin or integument of multicellular organisms provides an important barrier between internal tissues of such organisms and the planetary environments in which such organisms live. One of the most important properties of biological skin in contrast non-biological skin is that biological skin usually possesses self-sealability whereas non-biological usually does not.
Among the major components of mammalian skins are various types of biologically generated proteins. Biologically generated proteins are copolyamino acids which have been synthesized on cellular ribosomes with amino acid sequences that are directed by nucleic acids.
However, it was discovered previously that thermal proteins can be made simply by heating amino acids together in a flask for several hours (Fox et al., 1958). Such compounds and methods for their preparation are described in U.S. Pat. Nos. 3,052,655 and 3,076,790, by Fox et al.
Thermal copolyamino acids form a class of thermally engineered proteins (TEPs) because they possess amino acid sequences that have not been currently found in nature. They sometimes are referred to as proteinoids to reflect the fact that, although they resemble proteins structurally and functionally, they are produced abiotically in contrast to biologically generated proteins such as collagen, to use just one example. They are also referred to as thermal proteins for the same reason. Organisms do not make proteins by heating amino acids.
Proteinoids, or TEPS, are much easier to make than proteins which are engineered by genetic means or by standard organic synthetic means.
It was previously found that thermal copolyamino acids, upon being heated in aqueous solution and allowed to cool, spontaneously form microspheres approximately one micron in diameter (Fox, 1960). Such microspheres have been found to mimic many of the properties of biological cells.
The object of this invention was to make a self-sealing artificial skin from thermal copolyamino acids, or TEps, that could mimic some of the proerties of biological skins.
Amino acids were heat-polymerized to yield thermal copolyamino acids, also known as proteinoids or thermally engineered proteins (TEPs). When the TEPs were boiled in hot water and allowed to cool slowly to room temperature in an undisturbed fashion, all of the TEPs tested formed self-sealing artificial skins on the surface of the proteinoid solutions. Such artificial skins could be picked up and layered on the surface of an object by immersing the object in the solution and bringing it out of solution from underneath the artificial skin that had formed on the surface of the TEP solution.
Thermal copolyamino acid PB V 5 (1) was prepared as follows. L-Aspartic acid (100 g), L-glutamic acid (100 g), and an equimolar mixture (50 g) of L-alanine, L-arginine, L-cysteine, glycine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine, and L-valine, were mixed together and then placed in a flask. The flask containing the amino acid mixture was then heated in an oil bath at 190° C. for 6 hrs. under a nitrogen atmosphere.
Thermal copolyamino acid PB V 5 (2) was prepared in a similar fashion except that 100 g of L-aspartic acid, 100 g of L-glutamic acid, and 100 g of the equimolar basic neutral (BN) amino acid mixture referred to above was used.
Thermal copolyamino acid PB V 5 (3) was prepared in a similar fashion except that 50 g of L-aspartic acid, 50 g of L-glutamic acid, 50 g of BN mix, and 50 g of L-lysine hydrochloride was used.
Thermal copolyamino acid PB V 5 (4) was prepared in a similar fashion except that 50 g of L-aspartic acid, 50 g of L-glutamic acid, 50 g of BN mix, and 100 g of L-lysine hydrochloride was used and the flask was heated at 195° C. instead of 190° C.
For the sake of convenience, the PB V 5 (1) thermal copolyamino acid is also referred to as a 2:2:1 Asp:Glu:BN TEP, the PB V 5 (2) thermal copolyamino acid is referred to as a 1:1:1 Asp:Glu:BN TEP, the PB V 5 (3) thermal copolyamino acid is referred to as a 1:1:1:1 Asp:Glu:BN:Lys TEP, and the PB V 5 (4) thermal copolyamino acid is referred to as a 1:1:1:2 Asp:Glu:BN:Lys TEP.
Distilled water (1000 ml) was poured into each flask of the resulting glass-like materials. The flasks were stirred overnight. The thermal copolyamino acid mixtures were filtered with Buchner funnels and filter papers. Powdery insoluble fractions of the thermal copolyamino acids were retained by the filter papers. These water-insoluble fractions were left to air dry overnight. The 2:2:1 Asp:Glu:BN TEP and the 1:1:1 Asp:Glu:BN TEP were further dried under a vacuum for another night. The resulting yields of the various TEPs were: 75 g of 2:2:1 TEP, 11 g of 1:1:1 TEP, 11 g of 1:1:1:1 TEP, and 11 g of 1:1:1:2 TEP. With regard to the 1:1:1 TEP, the yield is lower than expected because some of the 1:1:1 preparation formed a tar-like liquid upon addition of water. This was discarded along with the soluble fraction.
Distilled water (1500 ml) was added to each of the water-insoluble TEP fractions (1.5 g-6.0 g) in 2000 ml beakers. The beakers were heated over a large Bunsen burner until the contents were vigorously boiling. At this point, sticky portions of the TEPs adhered to the sides of the beakers. These portions were discarded. The hot colored soutions were decanted into a second set of 2000 ml beakers. Then the hot solutions were poured into 8 in. by 8 in. square Pyrex baking dishes (500 ml per dish). The dishes were allowed to cool slowly to room temperature without being disturbed.
Results. After 24 hours, a dry artificial skin comprised of the various thermal copolyamino acids referred to previously formed on the surface of the solutions in the square Pyrex baking dishes. The TEP skins possessed the ability to self-seal themselves approximately 24 hours after holes of approximately 1-2 cm diamter had been deliberately made in the artificial TEP skins.
Properties of the Self-Sealing Artificial Skins. The TEP skins can be picked up and applied to the surface of any object which is placed in the TEP solution and gently lifted out of the TEP solution from underneath the surface of the TEP skin. The skin thereupon dries on the surface of the subject object. This procedure can be repeated a number of times to build up several laminate layers of the skin upon a subject object. It was also found that the thickness of the skin which forms upon the surface of the TEP solutions is proportional to the concentration of proteinoid used in the preparation of the hot TEP solution.
The self-sealing artificial TEP skins can be applied to any surface where a dry, biologically compatible surface barrier against foreign matter is desired. Such undesirable foreign matter includes dust, dirt, and microbes. Artificial skins of this type have many applications, among them the dressing of mammalian burn wounds.
Claims (5)
1. A self-sealing artificial skin consisting of copolyamino acids thermally polymerized from a mixture of the following alpha amino acids: aspartic acid, glutamic acid, lysine, alanine, arginine cysteine, glycine, histidine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.
2. A self-sealing artificial skin as described in claim 1 wherein the said copolyamino acids were thermally polymerized from a mixture of the following alpha amino acids: 2 parts aspartic acid, 2 parts glutamic acid, and 1 part an equimolar mixture of alanine, arginine, cysteine, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.
3. A self-sealing artificial skin as described in claim 1 wherein the said copolyamino acids were thermally polymerized from a mixture of the following alpha amino acids: 1 part aspartic acid, 1 part glutamic acid, and 1 part an equimolar mixture of alanine, arginine, cysteine, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.
4. A self-sealing artificial skin as described in claim 1 wherein the said copolyamino acids were thermally polymerized from a mixture of the following alpha amino acids: 1 part aspartic acid, 1 part glutamic acid, and 1 part an equimolar mixture of alanine, arginine, cysteine, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine, and 1 part lysine hydrochloride.
5. A self-sealing artificial skin as described in claim 1 wherein the said copolyamino acids were thermally polymerized from a mixture of the following alpha amino acids: 1 part aspartic acid, 1 part glutamic acid, and 1 part an equimolar mixture of alanine, arginine, cysteine, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine, and 2 parts lysine hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/373,503 US4996292A (en) | 1989-06-30 | 1989-06-30 | Self-sealing artificial skin comprising copoly-alpha-amino acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/373,503 US4996292A (en) | 1989-06-30 | 1989-06-30 | Self-sealing artificial skin comprising copoly-alpha-amino acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US4996292A true US4996292A (en) | 1991-02-26 |
Family
ID=23472672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US07/373,503 Expired - Fee Related US4996292A (en) | 1989-06-30 | 1989-06-30 | Self-sealing artificial skin comprising copoly-alpha-amino acid |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US4996292A (en) |
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